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Papers In Press, published online ahead of print July 16, 2005
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Department of Nutritional Sciences, Cornell University, Ithaca, NY 14853
Corresponding Author: dm43{at}cornell.edu
The term vitamin E denotes a family of tocopherol and tocotrienols, plant lipids that are essential for vertebrate fertility and health. The principal vitamin E form found in humans, RRR-a-tocopherol (TOH), is thought to protect cells by virtue of its ability to quench free radicals, and functions as the main lipid-soluble antioxidant. Regulation of vitamin E homeostasis occurs in the liver, where TOH is selectively retained while other forms of vitamin E are degraded. Through the action of tocopherol transfer protein (TTP), TOH is then secreted from the liver into circulating lipoproteins that deliver the vitamin to target tissues. Presently, very little is known regarding the intracellular transport of vitamin E. We utilized biochemical, pharmacological and microscopic approaches to study the intracellular transport of vitamin E in cultured hepatocytes. We observe that tocopherol•HDL complexes are efficiently internalized through the SR-BI scavenger receptor. Once internalized, tocopherol arrives within ~30 minutes at intracellular vesicular organelles, where it colocalizes with TTP, and with a marker of the lysosomal compartment (LAMP1), before being transported to the plasma membrane in a TTP-depdendent manner. We further show that intracellular processing of tocopherol involves a functional interaction between TTP and an ABC-type transporter.
Revised on June 23, 2005
Accepted on July 6, 2005
Intracellular trafficking of vitamin E in hepatocytes: Role of tocopherol transfer protein
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